The relationship of the hormone-sensitive adenylate cyclase system to regulatory processes in malignant cells, to the process of the malignant transformation, and to cell dedifferentiation will be studied. Also, the possible role of lymphoid cell adenyl cyclase in immune response and host resistance to tumor growth will be investigated. Studies of adenylate cyclase in malignant cells cultured in vitro will include relations to growth and cell cycle, influence of contact inhibition of growth, bases of differences from normal cells, and effect of transformation of normal cells by virus and carcinogens. Cell types will include those of hepatic, connective tissue, and lymphoid origin. Tumors produced by virus and chemicals in vivo will be studied both directly in vivo and with malignant and premalignant cells cultured subsequently in vitro. Adenylate cyclase levels and hormonal activation, cyclic 3'5-adenosine monophosphate levels and rates of degradation, cyclic nucleotide-dependent protein kinase levels, and influence of hormones on macromolecular synthesis and other metabolic processes will be studied. The adenylate cyclase system represents a control system which may provide a meaningful index of the functional state of a particular cell type. These studies should provide new information concerning cell regulation as it applies to the malignant cell. BIBLIOGRAPHIC REFERENCES: Ahn, H.S., Horowitz, S.G., Eagle, H., and Makman, M.H.: Influence of Cell Density and Serum on Cyclic Nucleotide Concentrations in Human Fibroblasts. Fed. Proc. 34, 260 (1975). Makman, M.H. and Keehn, E.: Adenylate Cyclase of Normal and Transformed Human Fibroblasts: Influence of Hormones and 2-Chloroadenosine. Fed. Proc. 34, 263, (1975).